Methotrexate Accord Healthcare Ireland (Methotrexate)

Methotrexate is a folate antagonist used in several disease categories, primarily inflammatory and oncologic conditions.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: improves skin lesions and reduces plaque formation.
• Acute lymphoblastic leukemia: induces remission by inhibiting malignant cell proliferation.
• Osteosarcoma: contributes to tumor size reduction and disease control.
• Ectopic pregnancy: terminates trophoblastic tissue growth in non‑uterine implantation.

• Methotrexate inhibits the enzyme dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate. This blockade reduces DNA, RNA and protein synthesis, leading to impaired cell replication, particularly in rapidly dividing immune cells and malignant cells. The drug also interferes with other enzymes involved in folate metabolism, contributing to its anti‑inflammatory and cytotoxic effects.

Methotrexate may cause a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Nausea and vomiting.
• Fatigue or weakness.
• Mouth sores (stomatitis).
• Low white blood cell count (leukopenia).
• Elevated liver enzymes.
• Hair thinning or loss.

Serious or Rare Side Effects

• Severe liver toxicity or fibrosis.
• Pulmonary fibrosis or severe pneumonitis.
• Life‑threatening bone marrow suppression (pancytopenia).
• Acute renal failure.
• Serious infections due to immunosuppression.
• Rare cutaneous reactions such as Stevens‑Johnson syndrome.

When using methotrexate, several safety considerations should be observed to minimize risk.

• Pregnancy contraindication: avoid use in pregnancy due to high risk of fetal malformations.
• Renal function monitoring: assess creatinine clearance before and during therapy.
• Liver function monitoring: perform regular liver enzyme tests.
• Blood count monitoring: conduct frequent complete blood counts to detect cytopenias.
• Concomitant drug review: avoid use with known interacting agents such as NSAIDs and penicillins.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze.

Methotrexate interacts with several medicines that can alter its efficacy or increase toxicity.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate toxicity.
• Penicillins (e.g., ampicillin): reduce renal clearance, raising serum levels.
• Sulfonamides: compete for renal excretion, enhancing toxicity.
• Live vaccines: risk of severe infection due to immunosuppression.
• Proton pump inhibitors (omeprazole): may increase methotrexate exposure.

Moderate Interactions (Monitor Closely)

• Warfarin: enhanced anticoagulant effect, monitor INR.
• Trimethoprim‑sulfamethoxazole: may increase myelosuppression, watch blood counts.
• Anticonvulsants (phenytoin, carbamazepine): may reduce methotrexate efficacy, adjust dose if needed.
• Alcohol: can exacerbate liver toxicity, advise limitation.
• Vitamin supplements containing folic acid: may reduce therapeutic effect, consider timing.